Thiophene-2,5-dicarboxylic acid derivatives

Synthesis of Thiophene-2,5-Dicarboxylic Acid Derivatives from Thiodiacetates... 

Hi) Carboxylic acids and derivatives. The haloform reaction on thienyl methyl ketones leads to thiophenecarboxylic acids, which can be treated with Raney nickel to produce the open-chain acids. This method has been used for the five-carbon homologation of carboxylic acids and to produce dicarboxylic acids (Scheme 51). Long-chain carboxylic acids may also be prepared by using dicarboxylic acid derivatives for the acylation of thiophenes (Scheme 52). In the synthesis of Queen substance, the precursor (213) has been generated by Raney nickel desulfurization of the appropriate thiophene-2-acetic acid derivative (79T329). 

The Hinsberg synthesis of thiophene derivatives describes the original condensation of diethyl thiodiglycolate and a-diketones under basic conditions which provides 3,4-disubstituted-thiophene-2,5-dicarboxylic acids upon hydrolysis of the crude ester product with aqueous acid. ... 

Very little work has been done on fluoro derivatives of thiophenes. 2-Fluorothiophene was obtained in low yield from treatment of 2-iodothiophene with arsenic trifluoride. The action of fluoroboric acid on thiophenediazonium salts was unsuccessful. It may be useful for the preparation of 4-, 5-, 6- or 7-fluorobenzo[6]thiophenes from the appropriate amines. However, these are more conveniently prepared from fluorine-substituted benzenethiols by ring-closure reactions. For example 4,5,6,7-tetrafluorobenzo[6 Jthiophene was obtained by decarboxylation of the corresponding 2,3-dicarboxylic acid (equation 99) prepared by condensation of pentafluorobenzenethiol with diethyl acetylenedicarboxylate (Section 3.15.3.4.1). 2-Fluorothiophene has been prepared from 2-thienyllithium using perchloryl fluoride, and 2-fluorobenzo[ Jthiophene from the 2-lithio derivative in a similar manner (Section 3.14.3.9.1). 

Thienothiophenes 1 and 2 with ethylmagnesium bromide afford organometallic derivatives that can be carbonated to form the 2-carboxylic acids identical with those prepared by oxidation of the 2-acetyl derivatives.19-21,26,218 Thieno[3,2-i]thiophene-2,5-dicarboxylic acid was obtained analogously in the reaction of thienothiophene 2, using an excess of ethylmagnesium bromide.218... 

Much more work was done on extended quinones. Syntheses of six parent compounds (159-164) has been accomplished by two methods. In the first approach, a Friedel-Crafts reaction between thiophene-3,4-dicarboxylic acid and benzene or thiophenes was used, and in the second one chromium trioxide oxidation of the corresponding acetoxy derivatives was applied (72JOC1712). These systems behave differently in the presence of excess lithium aluminum hydride and aluminum hydride. Compounds 161 and 162 were reduced to hydroquinones, compounds 160 and 163 were deoxygenated... 

The mass spectra of some formyl derivatives of 2-(2 -thienyl)indole have been elucidateThe electroreduction of 4-(2-thienyl)quinoxaline has been further investigated. The preparation of 2,5-bis(benzoxazolyl)-thiophens from thiophen-2,5-dicarboxylic acid has been patented... 

Various Carbocyclic Fused Systems.—l,3-diphenyl-4//-5,6-dihydrocyclo-penta[c]thiophen-c/5-4,6-dicarboxylic acid has been prepared by the reaction of the appropriate 1,4-diketo-derivative with phosphorus pentasulphide. The reaction of (169) with tolane gave (170). Acylation of 2-methoxy-... 

The treatment of aliphatic acids such as (36), (36a), (36b) with thionyl chloride leads to the formation of the thiophen derivatives (37), (37a), (37b). In particular, the formation of thiophen-2,5 dicarboxylic acid chloride in 63% yield from adipic acid is almost sensational. Through the... 

Polymers from Thiophen Derivatives.—The bifunctionality of thiophen and its potential availability in large quantities at a low price has for many years attracted the interest of polymer chemists. However, progress has been slow. 2,5-Dichlorothiophen has been polymerized to a solid in 93% yield on treatment with aluminium chloride and cupric chloride in carbon disulphide. The product is believed to be poly-5-chloro-2,3-thienylene. Thiophen-2,5-dicarboxylic hydrazide was prepared by the reaction of thiophen-2,5-dicarbonyl chloride with the corresponding dihydrazide and then cyclodehydrated to poly-(thienylene-[2,5]-alt-l,3,4-oxadiazolylene-[2,5]-amer) (258) by polyphosphoric acid. This polymer could also be obtained directly from thiophen-2,5-dicarboxylic acid and hydrazine in oleum. The polymers produced were investigated in view of their thermal stability and as polymeric organic semiconductors. The same research... 

In Figure 8.11 the isomeric urethane derived from ProDOT-OH (hydroxy-3,4-propylenedioxy-thiophene, 3,4-dihydro-2H-thieno[3,4-b][l,4]dioxepin-3-ol) instead of EDOT-CH2OH is also depicted (formula B). ProDOT-OH is a typical byproduct of EDOT-CH2OH when synthesized from epibromohydrin and 3,4-dihydrox5dhiophene-2,5-dicarboxylic acid esters, and it is difficult to separate. More synthetic details are given in Chapter 12. Due to the mixture of two components, the results must be considered as only tentative. 

Alkylacenaphthylenes (115), in which R is ethyl, n-propyl, or isopropyl, likewise give both dehydrogenation and bridging products on treatment with sulfur at 185°C the parent compound acenaphtho[l,2-b]thiophene 39), its 8-methyl (116, R = CH3 R = H m.p. 61.5°C) and 9-methyl derivative (116, R = H R = CH3 m.p. 127°C) are formed, respectively, in yields of 15%. 9 The methyl products were characterized by the formation of acetoxymercuri and benzoyl derivatives, wherein substitution was believed to occur in the thiophene ring. The structure of the 8-methyl-9-benzoyl derivative was verified by chromic acid oxidation to naphthalene-1,8-dicarboxylic anhydride. 

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